C3b/C4b Complement Receptor-like molecules and uses thereof

Abstract

Novel C3b/C4b CR-like polypeptides and nucleic acid molecules encoding the same. The invention also provides vectors, host cells, selective binding agents, and methods for producing C3b/C4b CR-like polypeptides. Also provided for are methods for the treatment, diagnosis, amelioration, or prevention of diseases with C3b/C4b CR-like polypeptides.

1. An isolated polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 2. 
     
     
       2. An isolated polypeptide comprising the amino acid sequence of the mature C3b/C4b CR-like polypeptide wherein the mature polypeptide comprises the amino acid sequence as set forth in SEQ ID NO:2, and optionally further comprises an amino-terminal methionine. 
     
     
       3. An isolated polypeptide comprising the amino acid sequence selected from the group consisting of:
 (a) the amino acid sequence as set forth in SEQ ID NO:2 with 1 to 100 conservative amino acid substitution(s), wherein the polypeptide has C3b/C4b complement receptor-like activity of the polypeptide set forth in SEQ ID NO:2; 
 (b) the amino acid sequence as set forth in SEQ ID NO:2 with 1 to 100 amino acid insertion(s), wherein the polypeptide has C3b/C4b complement receptor-like activity of the polypeptide set forth in SEQ ID NO:2; 
 (c) the amino acid sequence as set forth in SEQ ID NO:2 with 1–100 amino acid deletion(s), wherein the polypeptide has C3b/C4b complement receptor-like activity of the polypeptide set forth in SEQ ID NO:2; and 
 (d) the amino acid sequence as set forth in SEQ ID NO:2 with the modification of from 1 to 100 amino acids selected from the group consisting of (i) conservative substitution(s); (ii) insertion(s); and/or (iii) deletion(s), wherein the polypeptide has C3b/C4b complement receptor-like activity of the polypeptide set forth in SEQ ID NO:2. 
 
     
     
       4. An isolated polypeptide encoded by a nucleic acid sequence selected from the group consisting of:
 (a) a nucleotide sequence set forth in SEQ ID NO:1; 
 (b) a nucleotide sequence encoding the polypeptide as set forth in SEQ ID NO:2; 
 (c) a nucleotide sequence which hybridizes under stringent conditions to the complement of (a) or (b), wherein said stringent conditions comprise a final wash at 65° C. in 0.1×SSC and 0.1% SDS, wherein the nucleotide sequence encodes a polypeptide which has C3b/C4b complement receptor-like activity of the polypeptide set forth in SEQ ID NO:2. 
 
     
     
       5. A composition comprising the polypeptide of  claims 1 ,  2 ,  3 , or  4 , and a pharmaceutically acceptable formulation agent. 
     
     
       6. The composition of  claim 5  wherein the pharmaceutically acceptable formulation agent is a carrier, adjuvant, solubilizer, stabilizer, or anti-oxidant. 
     
     
       7. The composition of  claim 5  wherein the polypeptide comprises the mature amino acid sequence as set forth in SEQ ID NO: 2. 
     
     
       8. The polypeptide of  claim 1 ,  2 ,  3 , or  4 , which is covalently modified with a water-soluble polymer. 
     
     
       9. The polypeptide of  claim 8  wherein the water-soluble polymer is selected from the group consisting of polyethylene glycol, monomethoxy-polyethylene glycol, dextran, cellulose, poly-(N-vinyl pyrrolidone) polyethylene glycol, propylene glycol homopolymers, polypropylene oxide/ethylene oxide co-polymers, polyoxyethylated polyols, and polyvinyl alcohol. 
     
     
       10. A fusion polypeptide comprising the polypeptide of  claims 1 ,  2 ,  3 , or  4 , fused to a heterologous amino acid sequence. 
     
     
       11. The fusion polypeptide of  claim 10  wherein the heterologous amino acid sequence is an IgG constant domain or fragment thereof. 
     
     
       12. A C3b/C4b CR-like polypeptide produced by the process of culturing a host cell under suitable conditions to express the polypeptide and optionally isolate the polypeptide from the culture, wherein the host cell comprises a vector having a nucleic acid selected from the group consisting of:
 (a) the nucleotide sequence set forth in SEQ ID NO: 1; 
 (b) a nucleotide sequence encoding the polypeptide as set forth in SEQ ID NO: 2; 
 (c) a nucleotide sequence which hybridizes under stringent conditions to the complement of (a) or (b), wherein said stringent conditions comprise a final wash at 65° C. in 0.1×SSC and 0.1% SDS, wherein the nucleotide sequence encodes a polypeptide which has C3b/C4b complement receptor-like activity of the polypeptide set forth in SEQ ID NO:2.